WO2021137494A1 - Composition for preventing or treating diabetes comprising butyricimonas sp. strain as active ingredient - Google Patents

Abstract

The present invention relates to: a pharmaceutical composition for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance, the pharmaceutical composition comprising, as an active ingredient, a Butyricimonas sp. strain, a culture broth thereof, a concentrate thereof, a dried product thereof, or a combination thereof; a food composition for preventing or ameliorating diabetes, improving insulin resistance, controlling blood glucose, or ameliorating glucose tolerance, the food composition comprising, as an active ingredient, a Butyricimonas sp. strain, a culture broth thereof, a concentrate thereof, a dried product thereof, or a combination thereof; a health functional food comprising the food composition; a feed composition for preventing or ameliorating diabetes, improving insulin resistance, controlling blood glucose, or ameliorating glucose tolerance, the feed composition comprising, as an active ingredient, a Butyricimonas sp. strain, a culture broth thereof, a concentrate thereof, a dried product thereof, or a combination thereof; a method for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance, the method comprising administering the pharmaceutical composition to an individual; use of a composition for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance, improving insulin resistance, or controlling blood glucose, the composition comprising a Butyricimonas sp. strain; and use of a composition for preparing a drug for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance, the composition comprising a Butyricimonas sp. strain. The composition according to the present invention improves weight gain due to a high-fat diet, increased blood glucose, decreased glucose tolerance, and insulin resistance, and thus can be effectively used for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance.

Description

Composition for preventing or treating diabetes comprising a strain of butyricimonas sp. as an active ingredient

The present invention is butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dried product, or a pharmaceutical composition for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance comprising a combination thereof as an active ingredient; Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried product, or a food composition for preventing or improving diabetes comprising a combination thereof as an active ingredient, improving insulin resistance, controlling blood sugar or improving glucose tolerance; Health functional food containing the food composition; Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried product, or diabetes prevention or improvement, insulin resistance improvement, blood sugar control, or a feed composition for improving glucose tolerance comprising a combination thereof as an active ingredient; A method for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance comprising administering the pharmaceutical composition to an individual; Prevention or treatment of diabetes, hyperglycemia or impaired glucose tolerance, improvement of insulin resistance or glycemic control of the genus Butyricimonas ( Butyricimonas sp. ) Use of a composition comprising a strain; And diabetes, hyperglycemia or impaired glucose tolerance for the preparation of a medicament for the prevention or treatment of butyricimonas genus (Butyricimonas sp. ) It relates to the use of a composition comprising a strain.

Due to recent economic development and changes in eating habits, the incidence of metabolic diseases such as obesity, hyperlipidemia, arteriosclerosis, hyperinsulinemia, or diabetes is rapidly increasing in Korea, and the incidence rate is significantly higher than the level of developed countries such as the United States and Western European countries. is known to have increased.

Obesity, which is one of the metabolic diseases, is a phenomenon caused by an imbalance in energy intake and consumption. It refers to an excessive accumulation of fat in the body. It is widely used to cause chronic diseases such as high blood pressure, diabetes, and cardiovascular disease. is known It is caused by various causes, and is generally recognized to be caused by excessive caloric intake, endocrine disorders, lack of exercise, and genetic factors.

Diabetes mellitus is a disease in which carbohydrate metabolism is impaired due to insufficient insulin or poor sensitivity to insulin. Type 1 diabetes mellitus (insulin-dependent diabetes mellitus/IDDM) and non-insulin-dependent diabetes mellitus (also known as adult type diabetes) It is classified as type 2 diabetes, which is non-insulindependent diabetes mellitus/NIDDM).

On the other hand, high blood sugar symptoms appearing in obesity or diabetes may cause complications such as damage to each organ in the body or loss of function. Therefore, effective blood sugar control is important, and in general, diet, exercise, or drug use is recommended for blood sugar control. However, diet and exercise therapy have a limit in fundamentally blocking the rise in blood sugar, so it is common to combine drug therapy in which drugs such as insulin secretagogues or insulin sensitivity improvers are administered. For example, acarbose (Acarbose, Bayer AG) developed as an alpha-glucosidase inhibitor to slow the absorption of carbohydrates after a meal, sulfonylurea, an insulin secretagogue, repaglinide, nateglinide, And there are drugs in the class of insulin resistance improving agents, such as Biguanide and Thiazolidinedione or glitazone.

As such, the currently used drugs are mainly chemically synthesized products, but various side effects such as kidney or liver dysfunction and heart disease are reported, so interest in materials that can treat metabolic diseases derived from natural products is increasing. is the trend

As one of these materials, lactic acid bacteria are attracting attention, and specifically, a pharmaceutical composition for preventing or treating obesity or obesity-related diseases, including Lactobacillus plantarum WiKim0062 (Korea Patent Application Publication No. 10-2019-0051771) ) or Lactobacillus curvatus ( Lactobacillus curvatus ) A pharmaceutical composition for lowering blood cholesterol and inhibiting obesity, including hy7601 (Korean Patent No. 10-0996577), and the like have been developed. However, there is still a need for a technology related to lactic acid bacteria that is effective in treating diabetes or controlling blood sugar enough to be commercially successful.

Under this background, the present inventors have made intensive research efforts to develop an antidiabetic agent and a blood sugar control agent using a natural product-derived ingredient. As a result, the Butyricimonas sp. strain improves weight gain, hyperglycemia, reduced glucose tolerance symptoms and insulin resistance due to a high-fat diet. The present invention was completed by confirming that it can be usefully used for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance by showing the efficacy.

SUMMARY OF THE INVENTION The present invention aims to solve the above problems and other problems related thereto.

An exemplary object of the present invention is butyricimonas sp. strain, its culture medium, its concentrate, its dried product, or diabetes, hyperglycemia, or a pharmaceutical for the prevention or treatment of impaired glucose tolerance comprising a combination thereof as an active ingredient It is to provide an enemy composition.

Another exemplary object of the present invention is the genus Butyricimonas sp. strain, its culture medium, its concentrate, its dried product, or diabetes prevention or improvement, insulin resistance improvement, blood sugar control or Food composition for improving glucose tolerance; And to provide a health functional food comprising the composition.

Another exemplary object of the present invention is the genus Butyricimonas sp. strain, its culture medium, its concentrate, its dried product, or diabetes prevention or improvement, insulin resistance improvement, blood sugar control comprising a combination thereof as an active ingredient Or to provide a feed composition for improving glucose tolerance.

Another exemplary object of the present invention is to provide a method for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance, comprising administering the pharmaceutical composition to a subject.

Another exemplary object of the present invention is to prevent or treat diabetes, hyperglycemia or impaired glucose tolerance, improve insulin resistance or control blood sugar, butyricimonas genus ( Butyricimonas sp. ) It is to provide the use of a composition comprising a strain.

Another exemplary object of the present invention is to provide a use of a composition comprising a strain of Butyricimonas sp. for the manufacture of a medicament for the prevention or treatment of diabetes, hyperglycemia or impaired glucose tolerance.

The technical problem to be achieved according to the technical idea of the invention disclosed in this specification is not limited to the problem for solving the above-mentioned problems, and another problem not mentioned can be clearly understood by those skilled in the art from the description below. There will be.

This will be described in detail as follows. Meanwhile, each description and embodiment disclosed in the present application may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. In addition, it cannot be seen that the scope of the present application is limited by the detailed description described below.

One aspect of the present invention for achieving the above object is the genus Butyricimonas sp. strain, its culture medium, its concentrate, its dried product, or a combination thereof as an active ingredient Diabetes, hyperglycemia or prevention of impaired glucose tolerance Or it provides a pharmaceutical composition for treatment.

The term " Butyricimonas sp. " strain of the present invention refers to microorganisms present in the gastrointestinal tract of various mammals such as mice and humans, which corresponds to the gram-negative and anaerobic genera.

The Butyricimonas sp. strain of the present invention may be a live cell, a dead cell, or a combination thereof. Specifically, the dead cells may be dead cells by heat treatment, but is not limited thereto.

The butyricimonas sp . strain of the present invention is specifically Butyricimonas virosa (Butyricimonas virosa), butyricimonas faecihominis (Butyricimonas faecihominis), Butyricimonas paravirosa (Butyricimonas paravirosa), Butyricimonas synergistic (Butyricimonas synergistic) ), or Butyricimonas faecalis ( Butyricimonas faecalis ) It may be, more specifically, Butyricimonas virosa ( Butyricimonas virosa ) Or Butyricimonas synergistica ) It may be, but is not limited thereto.

The term "culture medium" or "culture" of the present invention refers to a medium containing by-products and strains generated through metabolism of the strain by culturing the strain in a medium, specifically, buty lysimonas spp. may mean a culture solution or culture of, and more specifically, may refer to a culture solution or culture of Butyricimonas virosa or Butyricimonas synergistica. In addition, the concentrate or dilution of the medium, the dried product obtained by drying the medium, the prepared or purified product of the medium, or a mixture thereof may also be included as an active ingredient in the composition of the present invention.

As used herein, the term “active ingredient” refers to a component that alone exhibits a desired activity, or can exhibit activity together with a carrier that is inactive by itself.

In the composition of the present invention, the active ingredient may be included in any amount (effective amount) according to the specific use, formulation, purpose of blending, etc. as long as it can exhibit preventive or therapeutic activity for diabetes, hyperglycemia, or impaired glucose tolerance. It may be determined within the range of 0.01 wt % to 99.9 wt % based on the total weight. The "effective amount" means that when the composition of the present invention is administered to an individual subject to the application of the composition of the present invention during the administration period as suggested by those skilled in the art, the intended functional, such as prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance; Refers to the amount of the active ingredient included in the composition of the present invention, which can exhibit a pharmacological effect. Such an effective amount can be determined empirically by one of ordinary skill in the art within the scope of ordinary skill in the art.

The pharmaceutical composition of the present invention may include, as an active ingredient, the number of 10 ¹ to 10 ¹² CFU bacteria, specifically 10 ⁶ to 10 ¹⁰ CFU bacteria, and more specifically, the Butyricimonas sp. strain having ^{10 8 CFU bacteria as an active ingredient.}

As used herein, the term "diabetes" refers to a type of metabolic disease such as insufficient insulin secretion or failure to function normally, and is characterized by high blood sugar in which the concentration of blood glucose increases, and causes various symptoms and signs due to high blood sugar and causes urine It means a disease that results in the excretion of glucose from The "diabetes" includes all types of diabetes, for example, type 1 diabetes, type 2 diabetes, and hereditary diabetes. Specifically, the diabetes may be type 2 diabetes, or may be obese diabetes accompanied by obesity symptoms that cause diabetes.

As used herein, the term "hyperglycemia" refers to a state in which blood sugar levels are abnormally high or a state in which a blood sugar control drug is taken.

As used herein, the term “impaired glucose tolerance” refers to a state in which the glucose processing ability of a living body is abnormally decreased.

As used herein, the term "insulin resistance" refers to a state in which the action of insulin, the most important biohormone, which overall regulates energy metabolism such as carbohydrates, lipids, and proteins, is lower than normal at physiological insulin concentrations.

The term "prevention" of the present invention refers to any action that inhibits or delays diabetes, hyperglycemia, or impaired glucose tolerance through administration of the pharmaceutical composition of the present invention, and the term "treatment" of the present invention refers to administration of the pharmaceutical composition of the present invention It means any action in which diabetes, hyperglycemia, or impaired glucose tolerance is improved, alleviated, or is beneficially altered. As used herein, the term “improvement” refers to any action in which diabetes, insulin resistance, or glucose tolerance is improved by administration of the composition.

The term "pharmaceutical composition" of the present invention means one prepared for the purpose of preventing or treating a disease, and each may be formulated in various forms according to a conventional method and used. For example, it may be formulated in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., depending on the route of administration, and may be formulated in the form of external preparations and sterile injection solutions. Specifically, the administration route may be any suitable route including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of the combination of two or more routes is a case in which two or more formulations of drugs according to the route of administration are combined. For example, one drug is first administered by an intravenous route and the other drug is secondarily administered by a local route.

Pharmaceutically acceptable carriers are well known in the art according to administration routes or formulations, and specifically, reference may be made to the pharmacopoeia of each country including the 'Korean Pharmacopoeia'.

The pharmaceutical composition of the present invention may be prepared in the form of a pharmaceutical composition for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance further comprising an appropriate carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition. , the carrier may include a non-naturally occurring carrier. Specifically, the pharmaceutical composition is formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively. can be used In the present invention, carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using diluents or excipients, such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose or lactose. It is prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc., which are commonly used simple diluents such as water and liquid paraffin, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

Specific formulations of pharmaceutical compositions are known in the art, and reference may be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). This document is considered a part of this specification.

The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as the formulation method, the patient's condition and weight, the patient's sex, age, degree of disease, drug form, administration route and period, excretion rate, reaction sensitivity, etc. It can be variously selected by those skilled in the art, and the dosage and frequency do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention may be administered to mammals such as rats, dogs, cats, cattle, horses, pigs, and humans through various routes, preferably humans. Any mode of administration may be contemplated, for example, but not limited to, administration by oral, intravenous, intramuscular or subcutaneous injection.

In one embodiment of the present invention, as a result of oral administration of Butyricimonas virosa or Butyricimonas synergistica to an obese mouse model having hyperglycemia induced by a high-fat diet, the effect of reducing fasting blood sugar, improving glucose tolerance and improving insulin resistance was shown. Bar, it was confirmed that it can be used as a pharmaceutical composition for the prevention or treatment of diabetes, hyperglycemia, or impaired glucose tolerance in Butyricimonas ( FIGS. 3 and 4 ).

Another aspect of the present invention for achieving the above object is the butyricimonas genus (Butyricimonas sp. ) strain, its culture, its concentrate, its dry product, or diabetes prevention or improvement, insulin comprising a combination thereof as an active ingredient Food composition for improving resistance, controlling blood sugar or improving glucose tolerance; And it provides a health functional food comprising the composition.

The terms “genus Butyricimonas”, “culture solution”, “active ingredient”, “diabetes”, “insulin resistance”, “prevention” and “improvement” of the present invention are the same as described above.

As used herein, the term “glycemic control” refers to any act of changing the blood glucose concentration in a subject to a normal value by administering the composition of the present invention.

As used herein, the term "improving glucose tolerance" refers to any action in which a subject's glucose tolerance is improved or improved by administering the composition of the present invention.

Food compositions of the present invention as the active ingredient, 10 ¹ to 10 ¹² CFU bacteria, in particular from 10 ⁶ to 10 ¹⁰ CFU bacteria, and more specifically may comprise a Pseudomonas sp butynyl receiver having a 10 ⁸ CFU bacteria.

If the 　food composition of the present invention can exhibit the effects of preventing or improving diabetes, improving insulin resistance, controlling blood sugar and improving glucose tolerance, it may contain the Butyricimonas spp. strain in various wt%, but specifically, the 　food composition of the Butyricimonas spp. It may be included in an amount of 0.001 to 99.9 wt%, specifically 0.01 to 99.9 wt%, based on the total weight of the.

In addition, the composition of the present invention may further include any compound or natural extract known to have the activity and safety has already been verified in the art in order to enhance the convenience of administration or intake, in addition to the active ingredient. .

Such compounds or extracts include compounds or extracts and pharmaceuticals listed in compendial documents such as pharmacopeias of each country ('Korean Pharmacopoeia' in Korea) and health functional food regulations of each country ('health functional food standards and specifications', announced by the Ministry of Food and Drug Safety in Korea). Each country's laws governing the manufacture and sale of compounds, extracts, and health functional foods that have been approved for items in accordance with the laws of each country (the 'Pharmaceuticals Act' in Korea) that regulate manufacturing and sales ('Health Functional Food Act' in Korea) Depending on the functionalities recognized compounds or extracts may be included.

As used herein, the term “food” refers to meat, sausage, bread, chocolate, candy, stacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcohol There are beverages, vitamin complexes, health functional 　foods, and health 　foods, and includes all foods in the normal sense.

The health food means a food having an active health maintenance or promotion effect compared to general food, and the health supplement food means a food for the purpose of health supplementation. In some cases, the terms health function 　 food, health food, and health supplement are preferred.

The term "health functional food" in the present invention is the same term as food for special health use (FoSHU), and in addition to nutrition, it is a food with high medical and medical effects processed to efficiently exhibit bioregulatory functions. it means. Here, "function (sex)" means to obtain a useful effect for health purposes such as regulating nutrients or physiological action with respect to the structure and function of the human body. The food of the present invention can be manufactured by a method commonly used in the art, and during the manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, if the formulation of the above 　 food is also a formulation that is recognized as a food, it can be manufactured without limitation. The 　 composition for food of the present invention can be prepared in various types of dosage forms, and unlike general drugs, 　 has the advantage that there are no side effects that may occur during long-term administration of the drug using food as a raw material, excellent portability, and the present invention Medical 　food can be consumed as an adjuvant for preventing or improving diabetes, improving insulin resistance, controlling blood sugar, or improving glucose tolerance.

Specifically, the health function 　 food is a food prepared by adding or encapsulating, powdering, suspension, etc., to food materials such as beverages, teas, spices, gums, and confectionery of the Butyricimonas genus strain. It means to bring a specific effect, but unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time using food as a raw material.

Since the 　food composition of the present invention can be consumed on a daily basis, it is very useful because it can be expected to prevent or improve diabetes, improve insulin resistance, control blood sugar, or improve glucose tolerance.

The food composition of the present invention may be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, and ionic beverages, processed oils such as milk and yogurt, gums, rice cakes, Korean sweets, bread, Foods such as confectionery and noodles, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, and the like can be manufactured into health functional food preparations. In addition, the food composition of the present invention may have any product classification in terms of legal and functional classification as long as it conforms to the enforcement regulations at the time of manufacture and distribution. For example, it is a health functional food according to the 'Health Functional Food Act' in Korea, or confectionery, beans, tea, and beverages according to each food type according to the Food Ordinance of the Korea 'Food Sanitation Act' (the 'Food Standards and Specifications' notified by the Ministry of Food and Drug Safety). , food for special use, and the like.

In addition, the food composition of the present invention may contain food additives in addition to the active ingredient. Food additives can be generally understood as substances that are added to and mixed with or infiltrated into food in manufacturing, processing or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be ensured. Food additives with guaranteed safety are limited in terms of ingredients or functions in the Food Additives Ordinance in accordance with the laws of each country that regulate the manufacture and distribution of food ('Food Sanitation Act' in Korea). In the Korean Food Additives Code (“Food Additive Standards and Specifications” notified by the Ministry of Food and Drug Safety), food additives are classified into chemically synthetic products, natural additives, and mixed preparations in terms of ingredients. These food additives are sweeteners and flavorants in terms of function. It is classified into an agent, a preservative, an emulsifier, an acidulant, and a thickener.

The sweetener is used to impart an appropriate sweetness to food, and natural or synthetic ones may be used. Preferably, a natural sweetener is used. Examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

The flavoring agent may be used to improve taste or flavor, and both natural and synthetic ones may be used. Preferably, it is a case where a natural thing is used. In the case of using a natural one, the purpose of nutritional enhancement in addition to flavor may be concurrently used. The natural flavoring agent may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, or the like, or obtained from green tea leaves, dandelion leaves, bamboo leaves, cinnamon, chrysanthemum leaves, and jasmine. In addition, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo biloba, etc. can be used. The natural flavoring agent may be a liquid concentrate or a solid extract. In some cases, a synthetic flavoring agent may be used, and the synthetic flavoring agent may include esters, alcohols, aldehydes, terpenes, and the like.

Calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. can be used as the preservative, and as the emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin and the like may be used, and acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like may be used. Acidulant may be added so that the food composition has an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to the purpose of enhancing the taste.

As the thickener, a suspending agent, a settling agent, a gel-forming agent, a bulking agent, and the like may be used.

The food composition of the present invention may contain, in addition to the food additives as described above, physiologically active substances or minerals known in the art for the purpose of supplementing and reinforcing functionality and nutrition and guaranteed stability as food additives. Examples of the physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, and the like. Minerals include calcium preparations such as calcium citrate, stearic acid Magnesium preparations, such as magnesium, iron preparations, such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc, etc. are mentioned.

The food composition of the present invention may contain the food additives as described above in an appropriate amount to achieve the purpose depending on the type of product, and with respect to other food additives that may be included in the food composition of the present invention, You can refer to the Food Additives Ordinance.

Another aspect of the present invention for achieving the above object is the butyricimonas genus (Butyricimonas sp. ) strain, its culture, its concentrate, its dried product, or diabetes prevention or improvement, insulin comprising a combination thereof as an active ingredient It provides a feed composition for improving resistance, controlling blood sugar or improving glucose tolerance.

The terms "Butyricimonas genus", "culture medium", "active ingredient" "diabetes", "insulin resistance", "prevention", "improvement", "glycemic control" and "improving glucose tolerance" of the present invention are as described above. .

As used herein, the term "feed" refers to any natural or artificial diet, one meal, etc., or a component of the one meal meal for animals to eat, ingest, digest or suitable for, and various types of feed known in the art. It can be manufactured with, and preferably, rich feed, roughage and/or special feed may be included.

Concentrated feed includes seed fruits including grains such as wheat, oats, and corn, bran including rice bran, wheat bran, and barley bran as by-products obtained from refining grains, soybeans, fluid, sesame, linseed, coco palm, etc. Fish-Soluble is a concentrated fish meal, fish waste, and fresh liquid obtained from fish meal, fish waste, and residual starch, which is the main component of starch residue, which is the remainder after removing starch from sweet potatoes and potatoes, which are by-products obtained from oil extraction. Animal feed such as dried whey, yeast, chlorella, and seaweed, which is the residue from the production of fish soluble), meat meal, blood meal, cow meal, skim milk powder, milk from milk, and casein from skim milk However, the present invention is not limited thereto.

For roughage, raw grass feed such as wild grasses, grasses and green cuttings, turnips for feed, beets for feed, root vegetables such as luther beargers, a type of turnip, raw herbs, green crops, grains, etc. are placed in a silo. Examples include, but are not limited to, silage, which is stored feed fermented with lactic acid after filling, wild grasses, hay obtained by cutting and drying grass, straw for breeding crops, and leaves of legumes. Special feed includes mineral feed such as oyster shells and rock salt, urea feed such as urea or its derivative diureide isobutane, supplementing ingredients that are easily lacking when only natural feed raw materials are mixed, or adding to the compounded feed to increase the storability of the feed. There are feed additives and dietary supplements, which are substances added in trace amounts, but are not limited thereto.

The feed composition for preventing or improving diabetes, improving insulin resistance, controlling blood sugar or improving glucose tolerance according to the present invention is a Butyricimonas genus (Butyricimonas sp. ) strain, in an appropriate effective concentration range according to various feed preparation methods known in the art, It can be prepared by adding a culture solution thereof, a concentrate thereof, a dried product thereof, or a combination thereof.

The feed composition according to the present invention is not particularly limited as long as it is an individual for the purpose of preventing or improving diabetes, improving insulin resistance, controlling blood sugar, or improving glucose tolerance, and any feed composition is applicable. For example, non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cattle, sheep, pigs, goats, etc., birds and fish can be applied to any object.

Another aspect of the present invention for achieving the above object provides a method for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance, comprising administering the pharmaceutical composition to an individual in a pharmaceutically effective amount.

As described above, the genus Butyricimonas sp. strain provided in the present invention, its culture medium, its concentrate, its dried product, or a combination thereof can be used as an active ingredient for diabetes, hyperglycemia or impaired glucose tolerance, so that the above The composition may be used to prevent or treat diabetes, hyperglycemia or impaired glucose tolerance.

The term "individual" of the present invention includes, without limitation, mammals, including rats, livestock, humans, and the like, which are likely to or have developed diabetes, hyperglycemia, or impaired glucose tolerance.

In the method of treating diabetes, hyperglycemia or impaired glucose tolerance of the present invention, the administration route of the pharmaceutical composition may be administered through any general route as long as it can reach the target tissue. Although the pharmaceutical composition of the present invention is not particularly limited thereto, it may be administered through routes such as oral administration and rectal administration, and in some cases may be administered by other routes depending on the purpose.

Another aspect of the present invention for achieving the above object is the prevention or treatment of diabetes, hyperglycemia or impaired glucose tolerance, improvement of insulin resistance or glycemic control, butyricimonas genus ( Butyricimonas sp. ) Use of a composition comprising a strain to provide. Another aspect of the present invention for achieving the above object is diabetes, hyperglycemia, or for the preparation of a medicament for the prevention or treatment of hyperglycemia or impaired glucose tolerance, butyricimonas genus ( Butyricimonas sp. ) Provides the use of a composition comprising a strain do.

The composition comprising the Butyricimonas sp. strain according to the present invention shows the efficacy of reducing body weight and fasting blood sugar, improving glucose tolerance and improving insulin resistance in an obese mouse model having hyperglycemia induced by a high-fat diet, diabetes, hyperglycemia Or it may have a preventive or therapeutic effect on impaired glucose tolerance.

1 shows an experimental schedule of administering a high-fat diet with a Butyricimonas virosa or Butyricimonas synergistica strain after inducing an obese mouse model having high blood sugar in a mouse with a high-fat diet.

Figure 2a is the final body weight of mice measured as a result of orally administered with a high-fat diet for 6 weeks with live or dead cells of Butyricimonas virosa or Butyricimonas synergistica after feeding the mice a high-fat diet for 10 weeks; . It was confirmed that the experimental group (HFD-LB and HFD-DB) in which Butyricimonas virosa or Butyricimonas synergistica was orally administered to a mouse model that gained weight on a high-fat diet lost less weight than the negative control group (HFD). RD is a normal control group, HFD is a negative control group induced with hyperglycemic disease due to a high-fat diet, HFD-LB is an experimental group administered with Butyricimonas virosa or Butyricimonas synergistica live bacteria after hyperglycemia induction with a high-fat diet, and HFD- DB is an experimental group administered with Butyricimonas virosa or Butyricimonas synergistica dead bacteria after hyperglycemia induction with a high-fat diet. In this case, *P<0.05 indicates statistical significance when compared to HFD.

Figure 2b is the amount of change in body weight of mice before administration of Butyricimonas virosa or Butyricimonas synergistica and after administration of Butyricimonas virosa or Butyricimonas synergy. It was confirmed that body weight was reduced when orally administered Butyricimonas virosa or Butyricimonas synergistica to a mouse model that gained weight on a high-fat diet. In this case, *P<0.05 indicates statistical significance when compared to HFD.

3 is a fasting blood glucose of mice measured as a result of oral administration of Butyricimonas virosa or Butyricimonas synergistica live or dead cells with a high-fat diet for 6 weeks after feeding the mice a high-fat diet for 10 weeks. It was confirmed that fasting blood glucose was reduced compared to the negative control group (HFD) when Butyricimonas virosa or Butyricimonas synergistica was orally administered to a mouse model induced by hyperglycemia with a high-fat diet. In this case, *P<0.05 indicates statistical significance when compared to HFD.

Figure 4a is a change in blood glucose after glucose administration measured as a result of oral administration of Butyricimonas virosa or Butyricimonas synergistica live or dead cells with a high-fat diet for 6 weeks after supplying a high-fat diet to mice for 10 weeks; . It was confirmed that glucose tolerance was improved compared to the negative control group (HFD) when Butyricimonas virosa or Butyricimonas synergistica was orally administered to a mouse model in which glucose tolerance was induced by a high-fat diet.

4B is an Area under the curve (AUC) of the blood glucose concentration shown in FIG. 4A. It was confirmed that glucose tolerance was improved compared to the negative control group (HFD) when Butyricimonas virosa or Butyricimonas synergistica was orally administered to a mouse model in which glucose tolerance was induced by a high-fat diet. In this case, *P<0.05 indicates statistical significance when compared to HFD.

5 is a blood insulin concentration measured as a result of oral administration of Butyricimonas virosa or Butyricimonas synergistica live or dead cells along with a high-fat diet for 6 weeks after feeding the mice a high-fat diet for 10 weeks. It was confirmed that insulin resistance was improved compared to the negative control group (HFD) when Butyricimonas virosa or Butyricimonas synergistica was orally administered to a mouse model induced by a high-fat diet. In this case, *P<0.05 indicates statistical significance when compared to HFD.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

Example 1: Butyricimonas virosa ( Butyricimonas virosa ) and Butyricimonas synergistica ( Butyricimonas synergistica ) Securing the strain

Butyricimonas virosa (Accession No. KCTC 15148) and Butyricimonas synergistica according to the present invention were purchased from the Center for Biological Resources (Korean Collection for Type Cultures). After inoculating Butyricimonas virosa in Columbia culture medium containing 5% horse serum, the bacteria were obtained by centrifugation after about 5 days. After the bacteria ^{were subdivided into 110 8} CFU, live cells were stored at -70° C. until administration, and dead cells were stored after treatment in an autoclave (121° C., 15LB, 15 minutes).

Experimental Example 1: Butyricimonas virosa ( Butyricimonas virosa ) and Butyricimonas synergistica ( Butyricimonas synergistica ) treatment effect on diabetes, hyperglycemia and impaired glucose tolerance in animal models of the strain

Experimental Example 1-1: Obese mouse model

As the experimental animals, male 5-week-old C57BL/6N mice were purchased from Samtako Co. Ltd. and acclimatized to the laboratory environment while freely supplying basic feed (10 kcal% fat, D12450B) and water for 7 days. For the experimental group, after inducing an obese mouse model with high blood sugar by starting a high-fat diet (60 kcal% fat) for 10 weeks, and consuming a high-fat diet for an additional 6 weeks, Butyricimonas virosa or Butyricimonas synergy once a day Stica was orally administered ( FIG. 1 ). During the experimental period, a normal control group eating a normal diet and a negative control group eating a high-fat diet were included.

The experimental groups were classified as follows:

① A normal control group (Regular diet, RD) eating a basic normal diet (10 kcal% fat);

② A negative control group (High-fat diet, HFD) consuming a high-fat diet (60 kcal% fat) for 16 weeks;

③ Experimental group (HFD-LB) in which the ^{Butyricimonas virosa or Butyricimonas synergistica live cells (1x10 8} CFU) of the present invention were orally administered once daily for the last 6 weeks while consuming a high-fat diet for 16 weeks;

④ The experimental group (HFD-DB) in which the ^{Butyricimonas virosa or Butyricimonas synergistica dead cells (1x10 8} CFU) of the present invention were orally administered once daily for the last 6 weeks while consuming a high-fat diet for 16 weeks.

During the last 6 weeks of the experiment period, while administering a high-fat diet and Butyricimonas virosa, or a high-fat diet and Butyricimonas synergistica, the effects of glycemic control, improvement of glucose tolerance and improvement of insulin resistance were observed.

All animal experiments were conducted with approval from the Animal Experimental Ethics Committee (IACUC) of Sahmyook University (SYUIACUC 2019-004).

Experimental Example 1-2: Confirmation of weight change

In order to confirm the weight loss effect of the butyricimonas sp. strain according to the present invention, the weight change was measured.

Specifically, after administration of Butyricimonas virosa or Butyricimonas synergistica, the weight of the mice was measured every week, and the weight difference between the control group and the experimental group was compared after the end of the experiment.

As a result, as shown in FIGS. 2a and 2b, HFD-LB and HFD-, which is an experimental group in which live and dead cells of Butyricimonas virosa or Butyricimonas synergistica were administered along with a high-fat diet for 6 weeks after ingestion of a high-fat diet It was confirmed that the final body weight of DB was lower than the final weight of the control group (HFD) ingesting only a high-fat diet (Fig. 2a), and it was found that after 6 weeks of butyricimonas administration, the body weight decreased compared to before butyricimonas administration. was confirmed (Fig. 2b).

Experimental Example 1-3: Confirmation of changes in fasting blood sugar

In order to confirm the glycemic control effect of the Butyricimonas sp. strain according to the present invention, the change in fasting blood glucose was measured.

Specifically, blood glucose was measured once every 2 weeks after administration of Butyricimonas virosa or Butyricimonas synergistica. After fasting for 12 hours, fasting blood glucose was measured using Accu-Chec Performa system, Roche.

As a result, as shown in FIG. 3 , compared to the HFD group ingesting a high-fat diet, blood sugar was lower in HFD-LB and HFD-DB, which are the experimental groups administered with live and dead cells of Butyricimonas virosa or Butyricimonas synergistica. It was confirmed that there was a significant decrease.

Experimental Example 1-4: Confirmation of change in glucose tolerance

In order to confirm the effect of the Butyricimonas sp. strain according to the present invention on the in vivo glucose processing ability, the change in blood glucose after glucose administration was measured.

Specifically, for glucose tolerance test, an intraperitoneal blood glucose tolerance test (IPGTT) of mice was performed 6 weeks after administration of Butyricimonas virosa or Butyricimonas synergistica. After intraperitoneal administration of glucose at a dose of 2 g/kg, blood was collected from the tail vein of mice at 0, 15, 30, 60 and 120 minutes, and blood glucose was measured with a glucometer.

As a result, as shown in FIGS. 4a and 4b, when compared to the HFD control group, the glucose processing rate of the HFD-LB and HFD-DB groups, which are live and dead cells of Butyricimonas virosa or Butyricimonas synergistica, is improved, It was confirmed that Butyricimonas virosa and Butyricimonas synergistica improved glucose tolerance by inhibiting insulin resistance induced by a high-fat diet.

Experimental Example 1-5: Confirmation of changes in insulin resistance

In order to confirm the effect of the Butyricimonas sp. strain according to the present invention on the improvement of insulin resistance in vivo, the fasting blood insulin concentration was measured.

Specifically, after 6 weeks of administration of Butyricimonas virosa or Butyricimonas synergistica, blood insulin concentrations were measured using the LBIS Mouse Insulin ELISA kit, and the difference between the control group and the experimental group was compared.

As a result, as shown in FIG. 5 , the blood of HFD-LB and HFD-DB, the experimental group in which live and dead cells of Butyricimonas virosa or Butyricimonas synergistica were administered along with a high-fat diet for 6 weeks after ingestion of a high-fat diet It was confirmed that the insulin concentration was measured lower than the insulin concentration of the control group (HFD) that consumed only the high-fat diet.

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention, rather than the above detailed description, all changes or modifications derived from the meaning and scope of the claims described below and their equivalents.

Claims (12)

1. Butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dry product, or a pharmaceutical composition for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance comprising a combination thereof as an active ingredient.
2. According to claim 1,

   The Butyricimonas genus ( Butyricimonas sp. ) The strain is a live cell, dead cell, or a pharmaceutical composition that is included in the form of a combination thereof.
3. According to claim 1,

   The butyric receiver Pseudomonas genus (Butyricimonas sp.) Strains butynyl receiver Pseudomonas birosa (Butyricimonas virosa), butynyl receiver Pseudomonas passive hoe varnish (Butyricimonas faecihominis), butynyl receiver Pseudomonas para birosa (Butyricimonas paravirosa), butynyl receiver Pseudomonas synergistic seutika (Butyricimonas synergistica ), and Butyricimonas faecalis ( Butyricimonas faecalis ), a pharmaceutical composition selected from the group consisting of.
4. According to claim 1,

   The pharmaceutical composition is characterized in that it exhibits an effect of lowering fasting blood sugar, an effect of improving glucose tolerance or an effect of improving insulin resistance, a pharmaceutical composition.
5. Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried product, or diabetes prevention or improvement, insulin resistance improvement, blood sugar control or food composition for improving glucose tolerance comprising a combination thereof as an active ingredient.
6. 6. The method of claim 5,

   The genus Butyricimonas ( Butyricimonas sp. ) The strain is a live cell, dead cell, or a food composition that is included in the form of a combination thereof.
7. 6. The method of claim 5,

   The butyric receiver Pseudomonas genus (Butyricimonas sp.) Strains butynyl receiver Pseudomonas birosa (Butyricimonas virosa), butynyl receiver Pseudomonas passive hoe varnish (Butyricimonas faecihominis), butynyl receiver Pseudomonas para birosa (Butyricimonas paravirosa), butynyl receiver Pseudomonas synergistic seutika (Butyricimonas synergistica ) and Butyricimonas faecalis ( Butyricimonas faecalis ) Selected from the group consisting of, a food composition.
8. A health functional food comprising the food composition of any one of claims 5 to 7.
9. Butyricimonas sp. strain, its culture medium, its concentrate, its dry product, or a combination thereof as an active ingredient, diabetes prevention or improvement, insulin resistance improvement, blood sugar control or a feed composition for improving glucose tolerance.
10. A method for preventing or treating diabetes, hyperglycemia, or impaired glucose tolerance, comprising administering the composition of any one of claims 1 to 4 to a subject.
11. Prevention or treatment of diabetes, hyperglycemia or impaired glucose tolerance, improvement of insulin resistance or blood sugar control, butyricimonas genus ( Butyricimonas sp. ) Use of a composition comprising a strain.
12. Diabetes mellitus, for the manufacture of a medicament for the prevention or treatment of hyperglycemia or impaired glucose tolerance, butyricimonas genus ( Butyricimonas sp. ) Use of a composition comprising a strain.

Images